EPHA8
protein-codingEPH receptor A8, the group of Sterile alpha motif domain containing|EPH receptors
Gene summary
This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]
- EEK
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPHA8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020526.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 2 | 5 | |||
| missense | 181 | 1 | 1 | 183 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 183 | 4 | 3 | 190 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065387.1 | 17 | MANE Select | |
| Ensembl | ENSP00000166244.3 | 17 | MANE Select | |
| RefSeq | NP_001006944.1 | 5 | Standard | |
| Ensembl | ENSP00000363775.4 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- EPH-Ephrin signaling
- Axon guidance
- EPHA forward signaling
Biological Process
- substrate-dependent cell migration
- cell adhesion
- transmembrane receptor protein tyrosine kinase signaling pathway
- axon guidance
- neuron remodeling
Molecular Function
- transmembrane receptor protein tyrosine kinase activity
- GPI-linked ephrin receptor activity
- transmembrane-ephrin receptor activity
- ATP binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- early endosome membrane
- neuron projection
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000166244
- Coding exons
- 17
- Length
- 40031
- Individuals with no LoFs
- 125665
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 83
- Defined
- 125748
- p
- 0.000330
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.707 | 642 | 694 | 0.924 | 0.0000493 | 6460 |
| Missense (PolyPhen) | 281 | 316.99 | 0.88646 | 2783 | ||
| Synonymous | 1.55 | 261 | 295 | 0.885 | 0.0000216 | 2099 |
| Loss of Function | 3.15 | 24 | 47.4 | 0.506 | 0.00000256 | 481 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.000096 | 0.000092 | rare |
| European (Non-Finnish) | 0.00028 | 0.00026 | rare |
| South Asian | 0.00067 | 0.00062 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI- anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.421
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.778
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |